The long-term career goal of the applicant, Amy H. Kao, MD, MPH, is to become an independent clinical investigator in the areas of rheumatology, immunology, and cardiovascular epidemiology. The candidate recently completed a Rheumatology Fellowship at the University of Pittsburgh School of Medicine and the Masters in Public Health degree in epidemiology from the University of Pittsburgh Graduate School of Public Health. She will now assume a position of Instructor of Medicine. She will strengthen her skills in clinical and translational research under the direction of her sponsors, Dr. Susan Manzi and Dr. Joseph Ahearn. Together they have designed a training plan that includes formal coursework in advanced areas of epidemiology and research design, participation in various seminars and lectures, and regular meetings with sponsors and mentors. They have assembled a strong group of research professionals to guide and assist Dr. Kao with her Career Development. Drs. Manzi and Ahearn are well-established and highly regarded physician scientists with a long record of successful mentoring who have combined their respective clinical and basic science expertise to form a novel clinical/translational research program in their newly created Lupus Center of Excellence. Dr. Kao has the full support of the Lupus Center as well as the Department of Medicine and Division of Rheumatology and Clinical Immunology. Dr. Kao's proposed research project is an outgrowth of three funded parent projects of Drs. Manzi and Ahearn and is aimed at examining biomarkers for lupus disease activity and investigating the role of complement in cardiovascular disease in lupus. Specifically, she intends to 1) determine the value of measuring erythrocyte-bound complement C4d (E-C4d) and erythrocyte-bound complement receptor I (E-CR1) in monitoring disease activity in patients with SLE; 2) determine the capacity of erythrocytes to serve as "time capsules" of past disease activity and of reticulocytes to serve as "instant messengers" of ongoing disease activity in patients with SLE; and 3) determine the association between complement C4-derived ligands on platelets and cardiovascular disease in SLE. Results are expected to lead to development of new laboratory tests for earlier and more accurate detection of SLE flares, prediction of cardiovascular disease, to expedite appropriate treatment, reduce unnecessary treatment, and aid in developing and assessing new therapies.